Two cells derived from the same culture, line, species, organism, organ, or tissue can differ in terms of their genotypes, phenotypes, or patterns of gene expression. Variation in such attributes from one cell to the next can be of biological or medical interest. Accordingly, methods for handling and interrogating individual cells are now widely employed in biomedical research and pharmaceutical development. Microfluidic devices have been adapted for single-cell manipulations because they allow liquids, for example cell culture media, to be passed through channels and chambers having dimensions comparable to those of single cells. In microfluidic devices, cells can be tracked, sorted, characterized, subjected to treatments, or lysed to harvest material they contain. Other manipulations of single cells in these devices are possible.
Metering the passage of cells one by one through microfluidic devices, for example from a storage reservoir to an analysis site, is technically challenging, in part because of cellular adhesion. This phenomenon is the tendency of some cells to adhere to nearby surfaces or to each other. Cellular adhesion is governed by adhesion proteins in the plasma membranes or cell walls of individual cells, and is crucial to intercellular interactions and tissue function in vivo. In microfluidic devices, however, cellular adhesion can result in the undesired immobilization of cells on the internal surfaces of channels and chambers. To deter cellular adhesion, these surfaces can be passivated through chemical treatments or the application of microscopic textures. Surface passivation can be costly, and a given treatment may work under only a small range of experimental conditions. Alternatively, the immobilization of a cell on a microfluidic surface can be reversed by applying a force to the cell or changing its chemical environment. These actions, unless performed gently, can perturb the properties of the cell that are to be measured downstream, or alter the complement of biological molecules to be harvested from the cell.